Novel tricyclic antagonists of the prostaglandin D 2 receptor DP2 with efficacy in a murine model of allergic rhinitis

BA Stearns, C Baccei, G Bain, A Broadhead…

Index: Stearns, Brian A.; Baccei, Christopher; Bain, Gretchen; Broadhead, Alex; Clark, Ryan C.; Coate, Heather; Evans, Jilly F.; Fagan, Patrick; Hutchinson, John H.; King, Christopher; Lee, Catherine; Lorrain, Daniel S.; Prasit, Peppi; Prodanovich, Pat; Santini, Angelina; Scott, Jill M.; Stock, Nicholas S.; Truong, Yen P. Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 16 p. 4647 - 4651

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Citation Number: 35

Abstract

The synthesis of a series of tricyclic antagonists for the prostaglandin D2 receptor DP2 (CRTH2) is disclosed. The activities of the compounds were evaluated in a human DP2 binding assay and a human whole blood eosinophil shape change assay. Potential metabolic liabilities of the compounds were addressed through in vitro CYP studies. The lead compound was demonstrated to have efficacy in a mouse model of allergic rhinitis ...